Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820212 | SCV000960913 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002221491 | SCV002498894 | uncertain significance | not provided | 2022-04-08 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24728327, 18822302, 21120944) |
| Ambry Genetics | RCV002426668 | SCV002740615 | likely benign | Hereditary cancer-predisposing syndrome | 2022-04-21 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| All of Us Research Program, |
RCV003997349 | SCV004819921 | uncertain significance | Lynch syndrome | 2023-11-28 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 849 of the MSH2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). To our knowledge, this variant has not been reported in individuals affected with MSH2-related disorders in the literature. This variant has been identified in 3/251452 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| ITMI | RCV000121565 | SCV000085759 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |